Amino Acid Polymorphism in HCHV Core Affects Infectious Virus Production and MHC Class I Molecule Expression

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KATO Takanobu 国立感染症研究所, ウイルス第二部, 室長 (20333370)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: HCV / インターフェロン / 薬剤耐性

Outline of Final Research Achievements

Amino acid polymorphisms in the HCV genotype 1b core protein has been reported to be a potent predictor for poor response to IFN-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of R/Q at aa 70 and L/M at aa 91. We found that the polymorphism at aa 70 was associated with efficiency of infectious virus production, and this deteriorated virus production in strains with aa70Q resulted in the intracellular accumulation of HCV proteins and attenuation of MHC class I molecule expression induced by IFN treatment through enhanced protein kinase R phosphorylation. These observations may explain the strain-associated resistance to IFN-based therapy and hepatocarcinogenesis of HCV.

Free Research Field

肝臓病学